A neuroepithelial wave of BMP signalling drives anteroposterior specification of the tuberal hypothalamus
Abstract
The tuberal hypothalamus controls life-supporting homeostatic processes, but despite its fundamental role, the cells and signalling pathways that specify this unique region of the CNS in embryogenesis are poorly characterised. Here we combine experimental and bioinformatic approaches in the embryonic chick to show that the tuberal hypothalamus is progressively generated from hypothalamic floor plate-like cells. Fate-mapping studies show that a stream of tuberal progenitors develops in the anterior-ventral neural tube as a wave of neuroepithelial-derived BMP signalling sweeps from anterior to posterior through the hypothalamic floor plate. As later-specified posterior tuberal progenitors are generated, early-specified anterior tuberal progenitors become progressively more distant from these BMP signals and differentiate into tuberal neurogenic cells. Gain- and loss-of-function experiments in vivo and ex vivo show that BMP signalling initiates tuberal progenitor specification, but must be eliminated for these to progress to anterior neurogenic progenitors. ScRNA-Seq profiling shows that tuberal progenitors that are specified after the major period of anterior tuberal specification begin to upregulate genes that characterise radial glial cells. This study provides an integrated account of the development of the tuberal hypothalamus.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file.All chick single-cell RNA-seq data have been deposited at GEO (GSE171649) and are publicly available.
Article and author information
Author details
Funding
Wellcome Trust (212247/Z/18/Z)
- Marysia Placzek
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Elisabeth Knust, Max-Planck Institute of Molecular Cell Biology and Genetics, Germany
Version history
- Received: August 31, 2022
- Preprint posted: September 2, 2022 (view preprint)
- Accepted: January 29, 2023
- Accepted Manuscript published: January 31, 2023 (version 1)
- Version of Record published: February 10, 2023 (version 2)
Copyright
© 2023, Chinnaiya et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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